JNJ 39758979

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

一种有效的、选择性的、口服生物可利用的组胺 H4 受体拮抗剂，Ki 为 12.5 nM。

A potent, selective, orally bioavailable histamine H4 receptor antagonist with Ki of 12.5 nM, >80-fold selectivity over other histamine receptors; shows dose-dependent activity in models of asthma and dermatitis, has good pharmacokinetics.Asthma Phase 2 Clinical.

JNJ 39758979 is a selective, high-affinity histamine H4 receptor antagonist with a Ki of 12.5 nM versus the human H4 receptor and functionally antagonizes histamine-induced cAMP inhibition with a pA2 of 7.9 in transfected cells. At the mouse H4R, the Ki=5.3 nM and the pA2=8.3. At the monkey H4R, the Ki=25 nM and the pA2=7.5. The affinity for the rat (Ki=188 nM, pA2 = 7.2) and guinea pig H4R (Ki=306 nM) is moderate, and JNJ 39758979 has little if any affinity for the dog H4R (Ki≥10 μM). The compound is highly selective for H4R, as it exhibits low affinity for the H1, H2, and H3 receptors.JNJ-39758979 is metabolically stable (t1/2 >120 min) when incubated in vitro with human, rat, dog, or monkey liver microsomes.

JNJ-39758979 (10 mg/kg; p.o.) treatment shows that the Cmax, t1/2 and F values are 0.3 μM, 7.5 hours, and 36%, respectively.JNJ-39758979 (2 mg/kg; i.v.) treatment shows that the Vss, AUC, CL and t1/2 were 19.9 L/kg, 1.4 μM*h, 2.2 L/h, and 2.1 hours, respectively . Animal Model:Sprague-Dawley rats Dosage:10 mg/kg Administration:Oral administration (Pharmacokinetic Analysis)Result:The Cmax, t1/2 and F values were 0.3 μM, 7.5 hours, and 36%, respectively.

JNJ-39758979 | JNJ39758979

GPCR/G Protein

Histamine Receptor

Histamine Receptor

Inflammation/Immunology

Asthma

1046447-90-8

221.308

C11H19N5

>98% (HPLC)

DMSO : 33.33 mg/mL 150.61 mM;

NC1=NC(C(C)C)=CC(N2C[C@H](N)CC2)=N1

(R)-4-(3-amino-pyrrolidin-1-yl)-6-isopropyl-pyrimidin-2-ylamine

(-20℃)

With Ice Pack

≥ 2 years